RGD Reference Report - Reaction mechanism and molecular basis for selenium/sulfur discrimination of selenocysteine lyase. - Rat Genome Database

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Reaction mechanism and molecular basis for selenium/sulfur discrimination of selenocysteine lyase.

Authors: Omi, Rie  Kurokawa, Suguru  Mihara, Hisaaki  Hayashi, Hideyuki  Goto, Masaru  Miyahara, Ikuko  Kurihara, Tatsuo  Hirotsu, Ken  Esaki, Nobuyoshi 
Citation: Omi R, etal., J Biol Chem. 2010 Apr 16;285(16):12133-9. doi: 10.1074/jbc.M109.084475. Epub 2010 Feb 17.
RGD ID: 12793035
Pubmed: PMID:20164179   (View Abstract at PubMed)
PMCID: PMC2852952   (View Article at PubMed Central)
DOI: DOI:10.1074/jbc.M109.084475   (Journal Full-text)

Selenocysteine lyase (SCL) catalyzes the pyridoxal 5'-phosphate-dependent removal of selenium from l-selenocysteine to yield l-alanine. The enzyme is proposed to function in the recycling of the micronutrient selenium from degraded selenoproteins containing selenocysteine residue as an essential component. The enzyme exhibits strict substrate specificity toward l-selenocysteine and no activity to its cognate l-cysteine. However, it remains unclear how the enzyme distinguishes between selenocysteine and cysteine. Here, we present mechanistic studies of selenocysteine lyase from rat. ESI-MS analysis of wild-type and C375A mutant SCL revealed that the catalytic reaction proceeds via the formation of an enzyme-bound selenopersulfide intermediate on the catalytically essential Cys-375 residue. UV-visible spectrum analysis and the crystal structure of SCL complexed with l-cysteine demonstrated that the enzyme reversibly forms a nonproductive adduct with l-cysteine. Cys-375 on the flexible loop directed l-selenocysteine, but not l-cysteine, to the correct position and orientation in the active site to initiate the catalytic reaction. These findings provide, for the first time, the basis for understanding how trace amounts of a selenium-containing substrate is distinguished from excessive amounts of its cognate sulfur-containing compound in a biological system.

Gene Ontology Annotations    Click to see Annotation Detail View

Biological Process
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
selenocysteine catabolic process involved_inIMP 12793035PMID:20164179CAFA 

Cellular Component
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
catalytic complex part_ofIDA 12793035PMID:20164179CAFA 

Molecular Function

Objects Annotated

Genes (Rattus norvegicus)
Scly  (selenocysteine lyase)


Additional Information